ABSTRACT We are resubmitting an improved and updated proposal requesting funds for the purchase of a Thermo Scientific Q Exactive HF Orbitrap LC-MS/MS system to be operated in the Mass Spectrometry Services (MSS) core facility in the Department of Chemistry. The MSS serves more than 90 research groups on the UF campus from twelve departments and colleges. More than 30 non-UF academic institutions and industrial companies also utilize the MSS facility. We are requesting this instrument because its capabilities are well suited for diverse range of research projects including large- and small-biomolecules, characterization of unknowns, and quantitative data on a single platform. The Q Exactive Plus LC-MS/MS is a tandem mass spectrometer that combines a quadrupole mass analyzer for precursor selection with a high-resolution/high mass accuracy Orbitrap mass analyzer. The complete system will include the optional Protein Mode for enhanced analysis of intact proteins and protein complexes, an UltiMate 3000 RSLCnano LC system, a Nanospray Flex Ion Source and tubing required to change the system between capillary and nano flow, Biopharma Finder 1.0, and Proteome Discoverer 2.1 Base and Quantitation. The fields of metabolomics, proteomics, and lipidomics are now recognized as playing a critical role in systems biology and are becoming the focus of the development of diagnostic tests, novel drug therapies, personalized medicine, and understanding of infectious diseases, cancer, and metabolic disorders. The proposed Q Exactive HF Orbitrap system will be used for measuring complex mixtures of proteins, peptides, lipids, metabolites and other biomolecules requiring ultra-high resolution tandem mass spectrometry for detection, identification, and quantitation of those complex mixtures. This data will in turn improve the outcomes of the health related goals of the projects assembled in this proposal, examples including: understanding traumatic brain injury; understanding the ubiquitin- proteasome in the treatment of human cancers including multiple myeloma and mantle cell lymphoma; understanding drug resistance to HIV-1 protease; studying Adeno-associated virus (AAV) as a delivery vehicle or vector for gene therapy; developing biosensors, bioseparation methods, targeted drug delivery, and cancer cell treatment by combining aptamers and nanomaterials; and developing and understanding the mechanism of anthelmintics.